Genes known to play important roles in a variety of immune processes have been genetically analyzed in several human families. Cloned DNA or cDNA corresponding to HLA class I, class II (DRAlpha, DRBeta, DQAlpha, DQBeta, DOAlpha, DOBeta and DPBeta) and class III (C4) genes and to T cell receptor Alpha and Beta chain genes were used as probes in Southern blotting analysis of DNA samples from the members of eight families. Restriction fragment length polymorphisms were observed with certain enzymes and could be assigned to haplotypes in the families. each of the families was known to include at least one individual who inherited a recombinant HLA haplotype. The present studies have made it possible to more precisely define the location of the crossover event in each recombinant haplotype and to localize DOBeta a new class II Beta chain gene within the HLA complex. Polymorphic restriction fragments hybridizing with a probe corresponding to the constant region of the T cell receptor Beta chain gene were observed to segregate in six of the eight families. Haplotype assignments could be made on the basis of these polymorphisms as well as with polymorphic fragments that hybridize to probes corresponding to variable (V) gene segments. Polymorphism in T cell receptor Alpha chain genes was observed to be located in V gene segments or the 3' untranslated region. these polymorphisms will provide useful markers that will facilitate linkage studies and genetic analyses of T cell function.